Ruiz F, Hernández J, Pérez D
Department of Pharmacology, University of Murcia, Medical School, Spain.
J Pharm Pharmacol. 1989 May;41(5):306-10. doi: 10.1111/j.2042-7158.1989.tb06462.x.
The effect of diazepam on ectopic cardiac automaticity has been examined in rats. We also investigated whether "central" or "peripheral type" benzodiazepine receptors are involved, as well as the role of calcium, on the possible effect of diazepam, by studying the interaction of this drug with either GABA, picrotoxin, RO 15-1788, PK 11195, diltiazem or Bay K 8644. A local injury of the rat isolated right ventricle produced a sustained abnormal rhythm which was completely abolished by diazepam (30-50 microM). This effect was not modified by the presence of either GABA (100 microM) picrotoxin (2 microM) or RO 15-1788 (5 microM) but it was reduced by the antagonist of "peripheral type" benzodiazepine receptors PK 11195 (0.1 microM). On the other hand the calcium channel blocker diltiazem (5 microM) and the calcium channel activator Bay K 8644 (3 nM), respectively, potentiated and reduced the effect of diazepam. It is concluded that diazepam effectively reduces ectopic cardiac automaticity in the rat. The "central type" benzodiazepine receptors are not involved in this effect, but it seems to be, at least, partially mediated by "peripheral type" receptors and is a calcium-dependent phenomenon.
已在大鼠中研究了地西泮对异位心脏自律性的影响。我们还通过研究该药物与γ-氨基丁酸（GABA）、印防己毒素、RO 15 - 1788、PK 11195、地尔硫䓬或Bay K 8644的相互作用，来调查“中枢型”或“外周型”苯二氮䓬受体是否参与其中，以及钙在地西泮可能的作用中的作用。大鼠离体右心室的局部损伤产生了持续的异常节律，地西泮（30 - 50微摩尔）可使其完全消除。GABA（100微摩尔）、印防己毒素（2微摩尔）或RO 15 - 1788（5微摩尔）的存在并未改变这种作用，但“外周型”苯二氮䓬受体拮抗剂PK 11195（0.1微摩尔）可使其作用减弱。另一方面，钙通道阻滞剂地尔硫䓬（5微摩尔）和钙通道激活剂Bay K 8644（3纳摩尔）分别增强和减弱了地西泮的作用。结论是，地西泮可有效降低大鼠的异位心脏自律性。“中枢型”苯二氮䓬受体不参与此作用，但似乎至少部分由“外周型”受体介导，且是一种钙依赖性现象。
